Sterol 14-Demethylase P450 Activity Expressed in Rat Gonads: Contribution to the Formation of Mammalian Meiosis-Activating Sterol

Yoshida, Yuzo; Yamashita, Chika; Noshiro, Mitsuhide; Fukuda, Masako; Aoyama, Yuri

doi:10.1006/bbrc.1996.0929

Cited by 40 publications

(25 citation statements)

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“…1) was induced in rat ovaries by pregnant mare serum gonadotropins [16], but whereas hCG treatment of the intact rat increased the P45014DM transcript in cultured follicles, eCG had no effect in vivo [17]. However, the accumulation of MAS above any critical or control level has not been verified.…”

Section: Introductionmentioning

confidence: 85%

Gonadotropin-Induced Accumulation of 4,4-Dimethylsterols in Mouse Ovaries and Its Temporal Relation to Meiosis1

Baltsen

2001

Biology of Reproduction

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The resumption of oocyte meiosis is triggered by a number of 4,4-dimethylsterols termed meiosis-activating sterols (MAS). The levels of meiosis active (follicular fluid [FF]-MAS and bull testes [T]-MAS) and inactive (lanosterol) 4,4-dimethylsterols, free cholesterol, and progesterone were determined in gonadotropin-primed prepubertal mouse ovaries in vivo by high-performance liquid chromatography. Ovaries responded to an ovulatory stimulation by increasing their content of 4,4-dimethylsterols but not of free cholesterol. The ovarian 4,4-dimethylsterol response was followed with regard to time and dose-response to the gonadotropins and the resumption of meiosis was evaluated using histologic sections. All 4,4-dimethylsterols accumulated in a time-dependent manner in gonadotropin-primed mice after a subsequent stimulation with hCG. The peak of 4,4-dimethylsterol accumulation appeared postmeiotically but coincided roughly with ovulation, and the resumption of meiosis was triggered when the intraovarian level of MAS was <20% of its maximum. The ovarian accumulation of progesterone preceded the 4,4-dimethylsterol accumulation. The FF-MAS accumulation displayed a dose-response maximum with respect to hCG, and a variation of the follicular priming regime revealed that, in contrast to progesterone production, 4,4-dimethylsterol accumulation is dependent on previous follicular growth beyond the gonadotropin-dependent stage. The FF-MAS was not liberated from esterified stores during the accumulatory response and appeared to be synthesized de novo from a precursor (or precursors) metabolically upstream to lanosterol. The data remain inconsistent with a model in which MAS is regarded as the physiological trigger of meiosis. The 4,4-dimethylsterol accumulation is suggested to influence maturation processes by affecting membrane sterol composition.

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Section: Introductionmentioning

confidence: 85%

Gonadotropin-Induced Accumulation of 4,4-Dimethylsterols in Mouse Ovaries and Its Temporal Relation to Meiosis1

Baltsen

2001

Biology of Reproduction

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“…The expression of CYP51 may also be regulated via two mechanisms: a combination of clock gene products such as DEC2 and DBP, and hormonal signals producing cAMP (Yoshida et al 1996). Considering all the above, DEC2 and DBP are involved in the circadian control of hepatic sterol metabolizing CYPs to various extents.…”

Section: Dec2 May Modulate the Circadian Expression Of Cyp8b And Cyp51mentioning

confidence: 99%

Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP

Noshiro¹,

Kawamoto²,

Furukawa

et al. 2004

Genes to Cells

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The mammalian master molecular clock consisting of several clock gene products in the suprachiasmatic nucleus (SCN) drives circadian rhythms in behaviour and physiology. Molecular clocks consisting of the same components also exist in various peripheral organs. DEC1 and DEC2, basic helix-loop-helix transcription factors, were recently reported to be involved in the central clock in the SCN. We examined the expression profile of DEC1 and DEC2 in the periphery and their roles in the regulation of oscillating target genes in the liver. Levels of DEC1 and DEC2 mRNA exhibited a day-night variation in various peripheral tissues of rats. In the liver, their expression was high during the subjective night. Transfection assays showed that DEC2, but not DEC1, suppressed the transcription of the cholesterol 7α α α α -hydroxylase gene ( CYP7A ), overwhelming the potent enhancement by D -site binding protein (DBP). Electrophoretic mobility shift assays indicated that DEC2 binds to the E-box (CACATG) at the -219/-214 region of CYP7A . The transcriptional activities of the other sterol metabolizing cytochorme P450s (Cyps), CYP8B and CYP51 , were also suppressed by DEC2 but not DEC1. DEC2, but not DEC1, works as a direct output mediator that transmits the circadian signals to the hepatic functions, including the CYP7A , CYP8B , and CYP51 expression.

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“…CYP51 produces so-called meiosis-activating sterols [274] that can activate LXRα [275] and possibly the ubiquitously expressed LXRβ [172] as well. The human CYP51 mRNA was suppressed by oxysterols in HepG2 and adrenal cells [276], while the rat CYP51 was induced by gonadotropin in the ovary [277], reminiscent of steroidogenic CYP regulation. Both mechanisms are currently unknown, but may involve NRs.…”

Section: Cholesterol Synthesis and Cyp51mentioning

confidence: 99%

Regulation of cytochrome P450 (CYP) genes by nuclear receptors

Honkakoski

NEGISHI

2000

Biochemical Journal

292

152

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Members of the nuclear-receptor superfamily mediate crucial physiological functions by regulating the synthesis of their target genes. Nuclear receptors are usually activated by ligand binding. Cytochrome P450 (CYP) isoforms often catalyse both formation and degradation of these ligands. CYPs also metabolize many exogenous compounds, some of which may act as activators of nuclear receptors and disruptors of endocrine and cellular homoeostasis. This review summarizes recent findings that indicate that major classes of CYP genes are selectively regulated by certain ligand-activated nuclear receptors, thus creating tightly controlled networks.

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Sterol 14-Demethylase P450 Activity Expressed in Rat Gonads: Contribution to the Formation of Mammalian Meiosis-Activating Sterol

Cited by 40 publications

References 0 publications

Gonadotropin-Induced Accumulation of 4,4-Dimethylsterols in Mouse Ovaries and Its Temporal Relation to Meiosis1

Gonadotropin-Induced Accumulation of 4,4-Dimethylsterols in Mouse Ovaries and Its Temporal Relation to Meiosis1

Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP

Regulation of cytochrome P450 (CYP) genes by nuclear receptors

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